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Human Endogenous Retrovirus Type W Envelope from Multiple Sclerosis Demyelinating Lesions Shows Unique Solubility and Antigenic Characteristics

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Virologica Sinica 2021年第5期36卷 1006-1026页

作者： Benjamin Charvet Justine Pierquin Joanna Brunel Rianne Gorter Christophe Que´tard Branka Horvat sandra amor Jacques Portoukalian Herve´Perron GeNeuro Innovation Lyon 69008France CIRI International Center for Infectiology ResearchINSERM U1111CNRS UMR5308University of LyonENS LyonFrance Universite´Claude Bernard Lyon 1 Lyon 69000France Department of Pathology Amsterdam UMCLocation VUMC1007 MB AmsterdamThe Netherlands ProteinSimple Abingdon OX143NBUK Centre for Neuroscience and Trauma Blizard InstituteBarts and London School of Medicine and DentistryQueen Mary University of LondonLondon E12ATUK

In multiple sclerosis(MS),human endogenous retrovirus W family(HERV-W)envelope protein,pHERV-W ENV,limits remyelination and induces microglia-mediated *** better understand its role,we examined the soluble pHERV-W antigen from MS brain lesions detected by specific ***-chemical and antigenic characteristics confirmed differences between pHERV-W ENV and ***-W ENV monomers and trimers remained associated with membranes,while hexamers self-assembled from monomers into a soluble macrostructure involving sulfatides in MS *** hexamers are stabilized by internal hydrophobic bonds and external hydrophilic ***-W studies in MS also suggest that this diffusible antigen may correspond to a previously described highmolecular-weight neurotoxic factor secreted by MS B-cells and thus represents a major agonist in MS *** methods are now needed to identify encoding HERV provirus(es)in affected cells *** properties and origin of MS brain pHERV-W ENV soluble antigen will allow a better understanding of the role of HERVs in MS *** present results anyhow pave the way to an accurate detection of the different forms of pHERV-W ENV antigen with appropriate conditions that remained unseen until now.

关键词： Multiple sclerosis(MS) Brain Antigen HERV-W Envelope Endogenous retrovirus MSRV-ENV Syncytin Demyelination Lipids Glycolipids Sulfatides Oligomer Hexamer

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Tocotrienol isoforms:The molecular mechanisms underlying their effects in cancer therapy and their implementation in clinical trials

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Journal of Integrative Medicine 2024年第1期22卷 1-11页

作者： Maria Younes Ghady Loubnane Christopher Sleiman sandra Rizk Department of Natural Sciences Lebanese American UniversityByblosLebanon

Tocotrienols are found in a variety of natural sources,like rice bran,annatto seeds and palm oil,and have been shown to have several health-promoting properties,particularly against chronic diseases such as *** incidence of cancer is rapidly increasing around the world,not only a result of continued aging and population growth,but also due to the adoption of aspects of the Western lifestyle,such as high-fat diets and low-physical *** literature provides strong evidence that tocotrienols are able to inhibit the growth of various cancers,including breast,lung,ovarian,prostate,liver,brain,colon,myeloma and pancreatic *** findings,along with the reported safety profile of tocotrienols in healthy human volunteers,encourage further research into these compounds’potential use in cancer prevention and *** current review provided detailed information about the molecular mechanisms of action of different tocotrienol isoforms in various cancer models and evaluated the potential therapeutic effects of different vitamin E analogues on important cancer hallmarks,such as cellular proliferation,apoptosis,angiogenesis and ***/PubMed and Scopus databases were used to identify recently published articles that investigated the anticancer effects of vitamin E derivatives in various types of cancer in vitro and in vivo along with clinical evidence of adjuvant chemopreventive *** an overview of pre-clinical studies,we describe several completed and ongoing clinical trials that are paving the way for the successful implementation of tocotrienols in cancer chemotherapy.

关键词： Vitamin E Tocotrienols Cancer Molecular mechanism Clinical trials

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Targeting KRAS in pancreatic cancer

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Oncology Research 2024年第5期32卷 799-805页

作者： sandra STICKLER BARBARA RATH GERHARD HAMILTON Institute of Pharmacology Medical University of ViennaViennaA-1090Austria

Pancreatic cancer has a dismal prognosis due to late detection and lack of efficient *** Kirsten rat sarcoma virus(KRAS)oncogene is mutated in up to 90%of all pancreatic ductal adenocarcinomas(PDACs)and constitutes an attractive target for ***,the most common KRAS mutations in PDAC are G12D(44%),G12V(34%)and G12R(20%)that are not amenable to treatment by KRAS G12C-directed cysteine-reactive KRAS inhibitors such as Sotorasib and Adagrasib that exhibit clinical efficacy in lung *** G12C mutant pancreatic cancer has been treated with Sotorasib but this mutation is detected only in 2%–3%of ***,the KRAS G12D-directed MRTX1133 inhibitor has entered clinical trials and more of such inhibitors are in *** other KRAS mutations may be targeted indirectly via inhibition of the cognate guanosine exchange factor(GEF)Son of Sevenless 1 that drives *** agents seem to provide the means to target the most frequent KRAS mutations in PDAC and to improve patient outcomes.

关键词： Pancreatic cancer PDAC KRAS SOS1 PROTAC

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Pandemic punch:SARS-CoV-2 hits pancreas

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1779-1780页

作者： Ninel Azoitei sandra Heller Alexander Kleger Institute of Molecular Oncology and Stem Cell Biology Ulm UniversityUlmGermany Division of Interdisciplinary Pancreatology Clinic of Internal Medicine IUniversity Hospital UlmUlmGermany

The COVID-19 pandemic has profoundly impacted global health systems,revealing the extensive repercussions of SARS-CoV-2 beyond respiratory ***,traditionally considered a respiratory virus,SARS-CoV-2’s showcased the ability to target multiple organ systems including pancreas,an organ crucial for regulating blood sugar levels and aiding digestion.

关键词： pancreas respiratory traditionally

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Development of PROTACS degrading KRAS and SOS1

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Oncology Research 2024年第8期32卷 1257-1264页

作者： GERHARD HAMILTON MARIE-THERESE EGGERSTORFER sandra STICKLER Institute of Pharmacology Medical University of ViennaVienna1090Austria

The Kirsten rat sarcoma virus—son of sevenless 1(KRAS-SOS1)axis drives tumor growth preferentially in pancreatic,colon,and lung ***,KRAS G12C mutated tumors can be successfully treated with inhibitors that covalently block the cysteine of the switch II binding pocket of ***,the range of other KRAS mutations is not amenable to treatment and the G12C-directed agents Sotorasib and Adragrasib show a response rate of only approximately 40%,lasting for a mean period of 8 *** approach to increase the efficacy of inhibitors is their inclusion into proteolysis-targeting chimeras(PROTACs),which degrade the proteins of interest and exhibit much higher antitumor activity through multiple cycles of ***,PROTACs have been developed based on KRAS-or SOS1-directed inhibitors coupled to either von Hippel-Lindau(VHL)or Cereblon(CRBN)ligands that invoke the proteasomal *** of these PROTACs show increased activity in vitro and in vivo compared to their cognate inhibitors but their toxicity in normal tissues is not *** CRBN PROTACs containing thalidomide derivatives cannot be tested in experimental *** to such PROTACS arises through downregulation or inactivation of CRBN or factors of the functional VHL E3 ubiquitin *** highly active KRAS and SOS1 PROTACs have been formulated their clinical application remains difficult.

关键词： Proteolysis-targeting chimeras(PROTACs) Kirsten rat sarcoma virus(KRAS) Son of sevenless 1(SOS1) Von Hippel-Lindau Cereblon

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Design multifunctional Mg–Zr coatings regulating Mg alloy bioabsorption

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Journal of Magnesium and Alloys 2024年第4期12卷 1461-1478页

作者： Zohra Benzarti Sandesh Itani JoséDavid Castro sandra Carvalho Ana Sofia Ramos University of Coimbra CEMMPREARISEDepartment of Mechanical EngineeringRua Luís Reis Santos3030-788CoimbraPortugal Laboratory of Multifunctional Materials and Applications(LaMMA) Department of PhysicsFaculty of Sciences of SfaxUniversity of SfaxSoukra Road km 3.5B.P.1171Sfax3000Tunisia

Magnesium(Mg)alloys are widely used for temporary bone implants due to their favorable biodegradability,cytocompatibility,hemocompatibility,and close mechanical properties to ***,rapid degradation and inadequate strength limit their *** overcome this,the direct current magnetron sputtering technique is employed for surface coating in Mg-based alloys using various zirconium(Zr)*** approach presents a promising strategy for simultaneously improving corrosion resistance,maintaining biocompatibility,and enhancing strength without compromising *** leveraging Mg’s inherent biodegradability,it has the potential to minimize the need for secondary surgeries,thereby reducing costs and *** paper is a systematic study aimed at understanding the corrosion mechanisms of Mg–Zr coatings,denoted Mg-xZr(x=0–5 at.%).Zr-doped coatings exhibited columnar growth leading to denser and refined structures with increasing Zr *** analysis confirmed the presence of the Mg(00.2)basal plane,shifting towards higher angles(1.15°)with 5 at.%Zr doping due to lattice parameter changes(i.e.,decrease and increase of“c”and“a”lattice parameters,respectively).Mg–Zr coatings exhibited“liquidphilic”behavior,while Young’s modulus retained a steady value around 80 GPa across all ***,the hardness has significantly improved across all samples’coating,reaching the highest value of(2.2±0.3)GPa for 5 at.%*** testing in simulated body fluid(SBF)at 37℃ revealed a significant enhancement in corrosion resistance for Mg–Zr coatings containing 1.0–3.4 at.%*** with the 5 at.%Zr coating which exhibited a corrosion rate of 32 mm/year,these coatings displayed lower corrosion rates,ranging from 1 to 12 mm/*** synergistic enhancement in mechanical properties and corrosion resistance,achieved with 2.0–3.4 at.%Zr,suggests potential ability for reducing stress shielding and controlled degradation performance,and consequentl

关键词： Mg-Zr coatings Magnetron sputtering Nanoindentation Corrosion resistance Bone implants

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Towards trustworthy multi-modal motion prediction:Holistic evaluation and interpretability of outputs

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CAAI Transactions on Intelligence Technology 2024年第3期9卷 557-572页

作者： sandra Carrasco Limeros Sylwia Majchrowska Joakim Johnander Christoffer Petersson MiguelÁngel Sotelo David Fernández Llorca Computer Engineering Department Polytechnic SchoolUniversity of AlcalaMadridSpain AI Sweden GothenburgSweden Zenseact AB GothenburgSweden Department of Electrical Engineering Linköping UniversityLinköpingSweden Chalmers University of Technology GothenburgSweden European Commission Joint Research CentreSevilleSpain

Predicting the motion of other road agents enables autonomous vehicles to perform safe and efficient path *** task is very complex,as the behaviour of road agents depends on many factors and the number of possible future trajectories can be consid-erable(multi-modal).Most prior approaches proposed to address multi-modal motion prediction are based on complex machine learning systems that have limited ***,the metrics used in current benchmarks do not evaluate all aspects of the problem,such as the diversity and admissibility of the *** authors aim to advance towards the design of trustworthy motion prediction systems,based on some of the re-quirements for the design of Trustworthy Artificial *** focus is on evaluation criteria,robustness,and interpretability of ***,the evaluation metrics are comprehensively analysed,the main gaps of current benchmarks are identified,and a new holistic evaluation framework is ***,a method for the assessment of spatial and temporal robustness is introduced by simulating noise in the perception *** enhance the interpretability of the outputs and generate more balanced results in the proposed evaluation framework,an intent prediction layer that can be attached to multi-modal motion prediction models is *** effectiveness of this approach is assessed through a survey that explores different elements in the visualisation of the multi-modal trajectories and *** proposed approach and findings make a significant contribution to the development of trustworthy motion prediction systems for autono-mous vehicles,advancing the field towards greater safety and reliability.

关键词： autonomous vehicles evaluation interpretability multi-modal motion prediction robustness trustworthy AI

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High-resolution multi-scale air pollution system:Evaluation of modelling performance and emission control strategies

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Journal of Environmental Sciences 2024年第3期137卷 65-81页

作者： Diogo Lopes Joana Ferreira sandra Rafael Ka In Hoi Xin Li Yuan Liu Ka-Veng Yuen Kai Meng Mok Ana Isabel Miranda Department of Environment and Planning&CESAM University of AveiroAveiroPortugal Department of Civil&Environmental Engineering Faculty of Science and TechnologyUniversity of MacaoMacao SARChina

A high percentage of the world's population lives in areas where air pollutant concentrations exceed the World Health Organization *** work aims to develop and test,a high-resolution multi-scale air pollution modelling system by integrating a set of adequate *** system is able to provide detailed air pollutant concentrations in urban areas and support air quality management strategies through a better identification of different atmospheric *** also allows furthering the design and assessment of air pollution control measures for a specific *** evaluate its performance and suitability,the system was applied to the Macao Special Administrative Region(SAR),China,one of the most densely populated areas on earth,during a winter period when this area is affected by high levels of Particulate Matter(PM).Although the developed system tends to underestimate the PM concentrations,it revealed a good performance in reproducing the temporal and spatial air pollution *** exceedances of the Chinese air quality standards were calculated and high population exposure to PM pollution was *** tested urban atmospheric emission reduction scenarios have shown air quality improvements,indicating that emission reduction measures at urban level should focus on the domestic ***,it is crucial to implement joint pollution prevention strategies with neighbouring regions to improve the air quality in Macao *** approach developed in this work can support policymakers in defining new strategies to reduce atmospheric pollution in urban areas.

关键词： Urban areas High-resolution emission inventory Particulate matter Population exposure

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碳酸酐酶附着膜在微藻直接空气碳捕集中的应用与固碳性能的强化

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西安交通大学学报 2024年第9期58卷 11-18页

作者：王睿龙李明佳 sandra KENTISH 西安交通大学能源与动力工程学院西安710049 西安交通大学热流科学与工程教育部重点实验室西安710049 北京理工大学机械与车辆工程学院北京100081 墨尔本大学化学工程学院澳大利亚帕尔维尔维多利亚州3010

为了解决低浓度直接空气碳捕集条件下微藻光生物反应器内CO_(2)传质效率差、溶解度低的问题,采用实验的方法制备了碳酸酐酶(CA)附着的尼龙纤维膜,利用CA催化转化CO_(2)为碳酸氢根的性质,提出了一种可以改善微藻溶液中CO_(2)溶解度及转... 详细信息

为了解决低浓度直接空气碳捕集条件下微藻光生物反应器内CO_(2)传质效率差、溶解度低的问题,采用实验的方法制备了碳酸酐酶(CA)附着的尼龙纤维膜,利用CA催化转化CO_(2)为碳酸氢根的性质,提出了一种可以改善微藻溶液中CO_(2)溶解度及转化率的新型光生物反应器,测试了该反应器放置CA附着尼龙纤维漂浮膜前后的微藻培养和固碳性能,并进一步探究了膜的开孔率及CA附着量对微藻固碳率的影响。实验结果表明:所制备的CA附着的尼龙纤维膜对CO_(2)转化速率提升了62.7%,通过耐久性测试,CA的活性在5个培养周期后仍保持良好,性能衰减仅为11.3%;与传统气石鼓气方式相比,提出的新型光生物反应器的微藻质量浓度提高了29.7%,固碳率提升了65%;随着膜开孔率的增加和透光率的增加,单位CA负载质量的固碳率提高,开孔面积占比24.75%的对照组的单位CA固碳率相比不开孔提高了13%。该研究为进一步提高微藻直接空气捕集的固碳率提供了一种新的方法。

关键词：微藻光生物反应器直接空气碳捕集碳酸酐酶尼龙纤维膜

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Jacob's Room:A New Form fora New Novel

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Journal of Foreign Languages and Cultures 2024年第1期8卷 80-91页

作者： sandra Guardini VASCONCELOS University of São Paulo

This article discusses the impact of the Post-Impressionist Exhibition that Roger Fry organized in London in 1910 on Virginia Woolf's ideas on the *** dissatisfaction with the state of the genre finds expression in her diary and in her criticism of the work of the Edwardian ***'s Room(1922),her first truly experimental novel,deploys some of the painterly techniques that the post-impressionist painters and vanguard movements of the 1910s *** represents a decisive step in her search for a new form for a new novel.

关键词： Jacob's Room Virginia Woolf essay experimental novel painting post-impressionism

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